Our overall goal is to perform experiments that will provide insight into the secretion of components of the extracellular lining of small airways and into factors that modulate and influence this process. More specifically we will study the regulation of Clara cell secretion with particular reference to the physiological factors (changes in tidal volume) that might trigger secretion. We expect to achieve this objective using combined morphological (electron microscopic morphometry), physiologic (manipulation of the isolated ventilated perfused lung and ventilation of anesthetized rats) and histochemcial techniques to study these processes in bronchiolar Clara cells. We anticipate that these experiments will generate information that will enlarge our understanding of the molecular and cellular basis for conducting airways function; this may eventually lead to work that will increase our understanding of small airways function in normal humans and in humans with diseases effecting small airways such as chromic bronchitis, asthma and emphysema.